Objective To investigate the protective effect of mild hypothermia on radiation?induced lung injury, and to compare the differences with the clinically used drug amifostine. Methods Seventy?five male Sprague Dawley rats were randomly divided into control, irradiation, amifostine, mild hypothermia prevention, and mild hypothermia treatment groups. All groups (except the control group) received a single?dose 20 Gy electron?beam full?chest irradiation. The amifostine group received an intraperitoneal amifostine injection(150 mg/ kg)at 30 min before irradiation. The hypothermia prevention group received mild body cooling initiated prior to irradiation(34 ±1℃)and continued for 6 h. The hypothermia treatment group received mild body cooling immediately after irradiation and continued for 6 h. Lung tissues were examined by histopathology and for collagen content. Serum levels of malondialdehyde and glutathione, and superoxide dismutase (SOD) activity, were examined at 14 d and 35 d after irradiation. Tumor necrosis factor α levels in the lung tissue homogenates, and apoptosis in the lung tissues, were also examined. Results Serum SOD activity decreased immediately after irradiation, and was significantly recovered in the mild hypothermia treatment group at 14 d recovery compared with the irradiation group ( P < 0. 05). Malondialdehyde content in the amifostine group and mild hypothermia intervention group were lower than the irradiation group at 14 d recovery ( P < 0. 05). TNF?α levels in the irradiation group were significantly increased at 6 h after irradiation, but were significantly reduced in the amifostine group and mild hypothermia treatment group ( P < 0. 05). Numbers of apoptotic cells in the irradiation group were significantly increased and widely distributed in the irradiation group, but were reduced in all intervention groups (there were no differences between the intervention groups). Conclusions Mild hypothermia can provide antioxidant, anti?inflammatory, and anti?apoptotic effects following radiation?induced lung injury in rats, to levels similar to that using the clinical drug amifostine.